Evaluation of combined BCG and SARS-CoV-2 vaccination for immune enhancement and lung protection in Syrian hamsters

SARS-CoV-2 (SCV2) has posed significant global challenges, necessitating improved immunization strategies to enhance protection and mitigate disease severity. Combining Bacille Calmette-Guérin (BCG) with SCV2 vaccine shows potential due to BCG's immunomodulatory properties and ability to induce trained immunity. This study evaluates the efficacy of a combined BCG and SCV2 vaccine regimen in enhancing immune responses, controlling viral load, and reducing lung pathology following a live SCV2 challenge in a Syrian hamster model. In this controlled, randomized study, hamsters were divided into six groups and immunized with various BCG and SCV2 vaccine regimens. Hamsters were randomized into six groups: Group A received a high dose of BCG (5 × 10⁶ CFU) plus SCV2 vaccine on Days 0 and 14; Group B (control) received PBS; Group C received BCG alone; Group D received SCV2 vaccine alone; Group E received a BCG/SCV2 combination on Day 0 and SCV2 booster on Day 14; Group F received a low BCG dose (5 × 10³ CFU) plus SCV2 on both days. Post-challenge, weight changes, lung histopathology, neutralizing antibody titers, and viral load were assessed using qRT-PCR, TCID₅₀, and histological scoring to evaluate immunogenicity, viral control, and tissue damage. Post-challenge, Group A (Combined BCG [5 × 10⁶ CFU] and SCV2 vaccine on Day 0 and Day 14 as a booster) demonstrated stable weights and the strongest neutralizing antibody titers, effectively suppressing viral replication and showing minimal lung pathology (P < 0.05). In contrast, the control group (B) exhibited significant weight loss, high viral loads, and severe lung damage. Groups C, D, E, and F showed varying degrees of immune responses and pathology, with Group F (BCG [5 × 10³ CFU]) performing better than others but less effectively than Group A. The present investigation findings highlight the potential of a combined BCG and SCV2 vaccination strategy with an emphasis on dose to provide robust protection against severe COVID-19 outcomes and underscore the role of BCG as an immunological adjuvant to improve vaccine efficacy.